The long term objectives of this project are to understand the molecular and cellular physiology of the synapse as a prerequisite for comprehending more complex aspects of nervous system function and dysfunction. This research will likely have implications for many areas of neurobiology including synaptic plasticity, information processing, behavior, addiction, neurodegeneration, and psychiatric disease. The starting point of this research is an existing collection of 13 Drosophila mutants identified on the basis of a photoreceptor synaptic transmission phenotype. Specific aims include: 1) extending phenotypic characterization to include synapse ultrastructure and neuromuscular electrophysiology, 2) molecular cloning of the genes corresponding to the most interesting mutants, and 3) determining the molecular identity and cellular functions of the corresponding proteins. The candidate for this Research Career Award, Dr. R. Steven Stowers, has previously carried out molecular and genetic studies of synaptic transmission in the labs of Drs. Thomas Schwarz and Corey Goodman. Through this award, Dr. Stowers will take advantage of the electrophysiology and optical imaging expertise of his proposed mentor, Dr. Ehud Isacoff at UC Berkeley, to better understand the nature of the defects in his synaptic transmission mutants. The training Dr. Stowers will acquire in applying these biophysical techniques to neurobiological problems will complement his already strong background in genetics and molecular and cellular biology. In addition, the workshops, seminar series, and excellent neuroscience community at UC Berkeley provide an outstanding neuroscience training environment. Through expanding and diversifying his skill set to include electrophysiology and optical imaging, Dr. Stowers will develop into a formidable, well rounded neuroscientist ideally positioned to achieve both his immediate career goal of obtaining a faculty position at a research university and his long-term career goal of making significant contributions to neurobiology.